pH-responsive nanoparticle assembly from peptide amphiphiles for tumor targeting drug delivery

In this paper, the peptide amphiphiles (PA) which consists of RGDSEEEEEEEEEEK as pH-sensitive segment and stearic acid as hydrophobic segment named RGDS-E₁₀-Lys(C₁₈) was successfully synthesized. TEM images showed that uniformly dispersed nanoparticles could be formed by PA molecules in pH 7.4 medium, however, disintegrated in pH 5.0 medium. Circular dichroism (CD) spectrum indicated that polypeptide adopted a random-coil conformation in neutral medium (pH 7.4). The CD signal was significantly attenuate for decreased solubility of PA in medium with pH 5.0. As expected, the prepared RGDS-E₁₀-Lys(C₁₈) assembly showed high pH-sensitive property which demonstrated a much more rapid drug release from micelles in tumor tissue (acidic environment) than in physiological environment (neutral environment). After DOX-loaded micelles incubated with tumor cells, the cytotoxicity of the micelles against Hela cells was increased obviously, indicating the great potential of micelles developed here as promising vehicle for targeted pH-responsive drug delivery.